Retinal Ganglion Cell Axon Regeneration Requires Complement and Myeloid Cell Activity within the Optic Nerve.

Axon regenerative failure in the mature CNS contributes to functional deficits following many traumatic injuries, ischemic injuries, and neurodegenerative diseases. The complement cascade of the innate immune system responds to pathogen threat through inflammatory cell activation, pathogen opsonization, and pathogen lysis, and complement is also involved in CNS development, neuroplasticity, injury, and disease. Here, we investigated the involvement of the classical complement cascade and microglia/monocytes in CNS repair using the mouse optic nerve injury (ONI) model, in which axons arising from retinal ganglion cells (RGCs) are disrupted. We report that central complement C3 protein and mRNA, classical complement C1q protein and mRNA, and microglia/monocyte phagocytic complement receptor CR3 all increase in response to ONI, especially within the optic nerve itself. Importantly, genetic deletion of C1q, C3, or CR3 attenuates RGC axon regeneration induced by several distinct methods, with minimal effects on RGC survival. Local injections of C1q function-blocking antibody revealed that complement acts primarily within the optic nerve, not retina, to support regeneration. Moreover, C1q opsonizes and CR3+ microglia/monocytes phagocytose growth-inhibitory myelin debris after ONI, a likely mechanism through which complement and myeloid cells support axon regeneration. Collectively, these results indicate that local optic nerve complement-myeloid phagocytic signaling is required for CNS axon regrowth, emphasizing the axonal compartment and highlighting a beneficial neuroimmune role for complement and microglia/monocytes in CNS repair.SIGNIFICANCE STATEMENT Despite the importance of achieving axon regeneration after CNS injury and the inevitability of inflammation after such injury, the contributions of complement and microglia to CNS axon regeneration are largely unknown. Whereas inflammation is commonly thought to exacerbate the effects of CNS injury, we find that complement proteins C1q and C3 and microglia/monocyte phagocytic complement receptor CR3 are each required for retinal ganglion cell axon regeneration through the injured mouse optic nerve. Also, whereas studies of optic nerve regeneration generally focus on the retina, we show that the regeneration-relevant role of complement and microglia/monocytes likely involves myelin phagocytosis within the optic nerve. Thus, our results point to the importance of the innate immune response for CNS repair.

Intake of Vegetables and Fruits and the Risk of Cataract Incidence in a Japanese Population: The Japan Public Health Center-Based Prospective Study.

BACKGROUND: Although the consumption of vegetables and fruits is reported to influence the risk of cataract, no prospective study of this association from Asia has yet appeared. Here, we investigated the association between vegetable and fruit intake and cataract incidence in a large-scale population-based prospective cohort study in Japan. METHODS: This study included 32,387 men and 39,333 women aged 45-74 years who had no past history of cataract and had completed a dietary questionnaire of the Japan Public Health Center-based Prospective Cohort Study. The incidence of cataract was evaluated after 5-year follow-up. We used multiple logistic regression analyses to estimate the sex-specific odds ratios (ORs), with adjustment for confounding factors. RESULTS: We identified 1,836 incident cataracts in 594 men and 1,242 women. In men, the OR for cataract was decreased with higher intake of vegetables (ORQ5 vs Q1, 0.77; 95% confidence interval [CI], 0.59-1.01; Ptrend across quartile categories = 0.03) and cruciferous vegetables (ORQ5 vs Q1, 0.74; 95% CI, 0.57-0.96; Ptrend = 0.02). In contrast, the OR for cataract was increased with higher intake of vegetables among women (ORQ5 vs Q1, 1.28; 95% CI, 1.06-1.53; Ptrend = 0.01). Green and yellow vegetable and fruit intake were not associated with cataract in either sex. CONCLUSIONS: This study suggests that vegetables may reduce the risk of cataract in men, but not in women.

Relation Between Body Mass Index and Dry Eye Disease: The Japan Public Health Center-Based Prospective Study for the Next Generation.

OBJECTIVE: To investigate the relation between body mass index (BMI) and dry eye disease (DED). METHODS: We conducted a cross-sectional questionnaire-based survey in 85,264 Japanese men and women aged 40 to 74 years who participated in the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT Study). Dry eye disease was defined as the presence of severe symptoms or clinical diagnosis. A multivariable logistic regression model was used to estimate the odds ratios (ORs) of DED associated with BMI and their two-sided 95% confidence intervals (CIs). We adjusted for age, cohort area, visual display terminal time, smoking status, alcohol intake, education status, income status, as well as history of hormone replacement therapy for women. RESULTS: Prevalence of DED was 23.4% (n = 19,985; 6,289 men, 13,696 women). Higher BMI was correlated with a lower prevalence of DED in a dose-response fashion, with an adjusted OR of DED (95% CI) per 1 kg/m2 increment of BMI of 0.98 (95% CI: 0.97-0.99) for men and 0.97 (95% CI: 0.97-0.98) for women. CONCLUSIONS: This large population-based study showed an inverse relationship between BMI and prevalence of DED in a Japanese population. Underestimation of DED is warned, especially for participants with high BMI.

Quantitative Assessment of the Retina Using OCT and Associations with Cognitive Function.

PURPOSE: To determine the association of retinal thickness with cognitive function in Japanese persons. DESIGN: Cross-sectional, population-based survey. PARTICIPANTS: A total of 1293 Japanese persons aged 65 to 86 years who resided in the Saku area in the Japan Public Health Center-Based Prospective Study participated in the eye and mental health screening. METHODS: Participants underwent comprehensive ophthalmic assessment, including fundus photography, measurement of intraocular pressure, and determination of refraction status. We assessed the thickness of the macular retinal nerve fiber layer (mRNFL), ganglion cell-inner plexiform layer (GC-IPL), and ganglion cell complex (GCC, which includes the retinal nerve fiber layer and GC-IPL), and the full thickness in the macula and peripapillary retinal nerve fiber layer (ppRNFL) using spectral-domain (SD) OCT. Cognitive tests consisted of the Mini-Mental State Examination, Wechsler Memory Scale Revised logical memory I/II subtest, clock drawing test, and Clinical Dementia Rating Scale. These were used to designate the participants in the following 3 groups: Normal, those with mild cognitive impairment (MCI), and those with dementia. Multivariable logistic regression models were used to analyze associations between retinal thickness and cognitive function after adjusting potential confounding factors. MAIN OUTCOME MEASURES: Association of retinal thickness with cognitive function. RESULTS: Among the 1293 potential subjects, 114 were excluded for a diagnosis of depression, 64 were excluded for retinal disease, and 140 were excluded for scanning errors or suboptimal OCT images. The remaining 975 participants (mean age, 73.2 years) were included in this analysis. Significant differences were found in the 3 groups in all layers and GCC thickness, but not in ppRNFL thickness. After adjusting for age, sex, educational status, and refraction, full macular thickness and GCC thickness were inversely associated with the presence of dementia, but ppRNFL thickness was not. Furthermore, GC-IPL, GCC, and full macular thicknesses were all associated with the presence of dementia in the inferior sectors. CONCLUSIONS: Macular thickness was associated with the presence of dementia, but ppRNFL was not. Our results suggest that OCT measurements of the macula could be superior to those of the ppRNFL in assessing neurodegenerative changes and a potentially useful diagnostic biomarker of cognitive function.

Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration.

Retinal ganglion cells (RGCs), the projection neurons of the eye, cannot regenerate their axons once the optic nerve has been injured and soon begin to die. Whereas RGC death and regenerative failure are widely viewed as being cell-autonomous or influenced by various types of glia, we report here that the dysregulation of mobile zinc (Zn2+) in retinal interneurons is a primary factor. Within an hour after the optic nerve is injured, Zn2+ increases several-fold in retinal amacrine cell processes and continues to rise over the first day, then transfers slowly to RGCs via vesicular release. Zn2+ accumulation in amacrine cell processes involves the Zn2+ transporter protein ZnT-3, and deletion of slc30a3, the gene encoding ZnT-3, promotes RGC survival and axon regeneration. Intravitreal injection of Zn2+ chelators enables many RGCs to survive for months after nerve injury and regenerate axons, and enhances the prosurvival and regenerative effects of deleting the gene for phosphatase and tensin homolog (pten). Importantly, the therapeutic window for Zn2+ chelation extends for several days after nerve injury. These results show that retinal Zn2+ dysregulation is a major factor limiting the survival and regenerative capacity of injured RGCs, and point to Zn2+ chelation as a strategy to promote long-term RGC protection and enhance axon regeneration.

Association between glaucoma severity and driving cessation in subjects with primary open-angle glaucoma.

BACKGROUND: The aim of this study, which included a baseline cross-sectional study and a 3-year follow-up prospective study, was to investigate the association between glaucomatous visual field damage and driving cessation in subjects with primary open-angle glaucoma (POAG). METHODS: A total of 211 POAG subjects divided into 3 groups according to POAG severity (mild, moderate, or severe) in the better eye were enrolled along with 148 control subjects; subjects were asked about changes in their driving status. In the 3-year follow-up study, 185 of the POAG subjects and 80 of the controls annually reported their driving status. Adjusted odds ratios and 95% confidence intervals for the prevalence and incidence of driving cessation were estimated with a multiple logistic regression model. RESULTS: In the original cross-sectional study, 11/148 (7%) members of the control group reported having given up driving over the previous 5 years; the corresponding figures for the mild POAG, moderate POAG, and severe POAG groups were 9/173 (5%), 0/22 (0%), and 5/16 (31%), respectively (p = 0.001, Fisher's exact test), with severe POAG found to be associated with driving cessation after adjustment for age, gender, systemic hypertension, and diabetes mellitus (odds ratio 11.52 [95% CI 2.87-46.35], ref. control, p = 0.001). In the follow-up study, the proportions of subjects who ceased driving were 1/80 (1.3%) in the control group, 8/152 (5.3%) in the mild POAG group, 5/22 (22.7%) in the moderate POAG group, and 2/11 (18.2%) in the severe POAG group (p = 0.001, Fisher's exact test). Moderate POAG and severe POAG in the better eye were found to be associated with driving cessation after adjustment for age, gender, systemic hypertension, and diabetes mellitus (moderate POAG in the better eye: odds ratio 37.7 [95% CI 3.7-383.8], ref. control, p = 0.002, and severe POAG in the better eye: odds ratio 52.8 [95% CI 3.5-797.0], ref. control, p = 0.004). CONCLUSION: Moderate and Severe POAG in the better eye is associated with driving cessation.

Factors associated with developing a fear of falling in subjects with primary open-angle glaucoma.

BACKGROUND: To investigate the relationship between clinical risk factors, including visual field (VF) defects and visual acuity, and a fear of falling, among patients with primary open-angle glaucoma (POAG). METHODS: All participants answered the following question at a baseline ophthalmic examination: Are you afraid of falling? The same question was then answered every 12 months for 3 years. A binocular integrated visual field was calculated by merging a patient's monocular Humphrey field analyzer VFs, using the 'best sensitivity' method. The means of total deviation values in the whole, superior peripheral, superior central, inferior central, and inferior peripheral VFs were calculated. The relationship between these mean VF measurements, and various clinical factors, against patients' baseline fear of falling and future fear of falling was analyzed using multiple logistic regression. RESULTS: Among 392 POAG subjects, 342 patients (87.2%) responded to the fear of falling question at least twice in the 3 years study period. The optimal regression model for patients' baseline fear of falling included age, gender, mean of total deviation values in the inferior peripheral VF and number of previous falls. The optimal regression equation for future fear of falling included age, gender, mean of total deviation values in the inferior peripheral VF and number of previous falls. CONCLUSION: Defects in the inferior peripheral VF area are significantly related to the development of a fear of falling.

Factors associated with the occurrence of a fall in subjects with primary open-angle glaucoma.

BACKGROUND: The aim of the study is to investigate risk factors for future falls in subject with primary open angle glaucoma (POAG). METHODS: All participants answered the following question at their baseline ophthalmic examination: Have you had any falls in the last year? (Yes/No). All study participants answered the same question every 12 months for 3 years. The means of total deviation values in the whole, superior peripheral, superior central, inferior central, and inferior peripheral visual fields (VF) were calculated. The relationship between these mean VF measurements, and various clinical factors against patients' future falls was analyzed using multiple linear regression. RESULTS: Two-hundred ninety four POAG patients answered the baseline and follow-up fall questionnaires over a period of three years. Among 294 subjects, 69 patients experienced a fall during the three-year follow-up. History of falls at baseline (coefficient = 1.22), history of fear of falling at baseline (0.53), best corrected visual acuity in the worse eye (7.37), prevalence of diabetes mellitus (0.60), prevalence of systemic hypertension (0.53) were selected in the optimal model. CONCLUSIONS: Visual acuity in the worse eye, history of falls, fear of falling, diabetes mellitus, and systemic hypertension are risk factors for falling in subjects with POAG.

Driving self-restriction and motor vehicle collision occurrence in glaucoma.

PURPOSE: To confirm that subjects with primary open-angle glaucoma (POAG) who avoid driving in high-risk situations are less likely to be involved in motor vehicle collisions (MVCs) than those who do not. METHODS: This study evaluated 252 consecutive Japanese aged between 40 and 85 years with POAG. All participants were requested to answer a questionnaire on their driving habits, including self-restriction in driving at night, in rain, in fog, on freeways, and lane changing, and history of MVCs. Those who reported restricting their driving in one or more ways constituted the self-restriction group, and those who reported no self-restriction made up the no-restriction group. The prevalence of MVCs and the crash rate (number of MVCs/10,000 km driven) were compared between the two groups. The association between prevalence of MVCs and the number of driving self-restrictions was also evaluated. RESULTS: The association between driving self-restriction and MVCs was observed among the male subjects, not among the female subjects. Among the male subjects, the prevalence of MVCs was significantly higher in the no-restriction group than in the self-restriction group (no-restriction group, 33/107 = 30.8%; self-restriction group, 9/66 = 13.6%, p = 0.01). The crash rate was also significantly higher in the no-restriction group (no-restriction group, 1.4 ± 0.8; self-restriction group, 0.4 ± 0.3, average ± SE, p = 0.01). No restriction was significantly associated with MVCs (multivariable-adjusted odds ratios, 2.43 [95% confidence interval, 1.03 to 5.73]). The number of driving self-restrictions was also associated with MVCs (multivariable-adjusted odds ratios, 0.41 [95% confidence interval, 0.18 to 0.99], per one increment of self-restriction). CONCLUSIONS: Driving self-restriction may be associated with a reduced prevalence of MVCs in men with POAG.

Atp6ap2/(pro)renin receptor interacts with Par3 as a cell polarity determinant required for laminar formation during retinal development in mice.

(Pro)renin receptor [(P)RR], also known as Atp6ap2, has attracted growing attention as a key molecule for tissue renin-angiotensin system (RAS). In addition to its role in tissue RAS activation, Atp6ap2/(P)RR was originally identified as an accessory subunit for vacuolar H(+)-ATPase (v-ATPase), which is a multisubunit proton pump involved in diverse and fundamental cellular physiology. In this study, to elucidate the physiological function of Atp6ap2/(P)RR during retinal development in mammals, we used Cre-LoxP system to generate photoreceptor-specific conditional knock-out (CKO) mice, and revealed a critical role of Atp6ap2/(P)RR in photoreceptor development. Deletion of photoreceptor Atp6ap2/(P)RR did not affect retinal cell differentiation, but led to laminar disorganization around the outer nuclear layer together with severe dysfunction of photoreceptor cells. In the CKO mice, cell adhesion and polarity molecules, some of which were colocalized with Atp6ap2/(P)RR at the apical edge of the wild-type developing retina, were substantially dispersed together with mislocalization of retinal progenitor cells apart from the apical surface. Among theses molecules, coimmunoprecipitation using retinal homogenates and ATP6AP2/(P)RR-transfected cells showed that Atp6ap2/(P)RR interacted with partitioning defective 3 homolog (PAR3) protein, which is known to function in the Par-atypical protein kinase C (aPKC) system. Furthermore, yeast two-hybrid assays demonstrated direct molecular interaction between ATP6AP2/(P)RR and PAR3. Our present data revealed the novel function of Atp6ap2/(P)RR required for laminar formation during retinal development. We propose that this cellular activity associated with the Par-aPKC system, in addition to the v-ATPase function and tissue RAS activation, is the third biological role of Atp6ap2/(P)RR.

Biological effects of blocking blue and other visible light on the mouse retina.

BACKGROUND: To elucidate the biological effects of blocking fluorescent light on the retina using specific blocking materials. METHODS: Seven- to 8-week-old BALB/c mice were divided into three groups and placed in one of the three boxes: one blocked ultraviolet and violet wavelengths of light (violet blockade), one blocked ultraviolet, violet, blue and some other visible wavelengths (blue-plus blockade), and one allowed most visible light to pass through (control). They were then exposed to a white fluorescent lamp for 1 h at 5.65E-05 mW/cm(2) /s. After treatment, the electroretinogram, retinal outer nuclear layer thickness and retinal outer segment length were measured. In addition, retinal apoptotic cells were quantified by TdT-mediated dUTP nick-end labelling assay and c-Fos messenger RNA, and protein levels were measured by real-time reverse-transcription polymerase chain reaction and immunoblot analyses, respectively. RESULTS: The blue-plus blockade group retained a significantly better electroretinogram response following light exposure than the control or violet blockade groups. The blue-plus blockade group also exhibited greater outer nuclear layer thickness and greater outer-segment length, and fewer apoptotic cells after light exposure than the other groups. The c-Fos messenger RNA and protein levels were substantially reduced in the blue-plus blockade group and reduced to a lesser extent in the violet blockade group. CONCLUSIONS: The blockade of blue plus additional visible wavelengths of light was most effective in protecting the retina from light-induced damage. The blockade of violet light alone was also effective in reducing intracellular molecular responses, but these effects were not sufficient for attenuating retinal degeneration.

Dry eye disease is associated with deterioration of mental health in male Japanese university staff.

Dry eye disease (DED) is defined as a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear-film instability, with potential damage to the ocular surface. It is thought to be associated with reduced quality of life (QOL). The aim of the present study was to investigate the effects of DED on health-related QOL in Japanese university sedentary office workers who are daily users of visual display terminal. In this study, 163 university staff (99 male and 64 female), aged 23-69 years, served as study subjects. Subjects were asked to answer the following three questions. (1) How often do your eyes feel dry? (2) How often do your eyes feel irritated? (3) Have you ever been diagnosed by a clinician as having dry eye syndrome? Sixty-eight subjects who answered "constantly," "often", or "sometimes" to both questions 1 and 2 were classified as the DED Group, and the remaining 95 were defined as the Non-DED Group. QOL was assessed by the SF-36 questionnaire, which consisted of 36 items to produce three summary scores, namely, mental, physical, and role/social component summary scores. For males, the DED Group had significantly lower scores than the Non-DED Group for mental component summary (MCS) (P = 0.005). In multiple regression analysis, MCS scores were adversely related to DED in males (P = 0.015). DED was associated with worsened QOL. DED should be regarded as a factor that can lead to deterioration of mental health.

Visualization of distribution in the vitreous cavity via eye drops using ultra-heavily T2-weighted sequences in MRI: a preliminary study with enucleated pig eyes.

We investigated whether magnetic resonance imaging can visualize the distribution in the vitreous cavity via eye drops of ophthalmic solutions, gadolinium-based contrast agent, and 17O-water, and to clarify the usefulness of ultra-heavily T2-weighted sequences in the research of intraocular distribution. Five different solutions (V-ROHTO, TRAVATANZ, gadobutrol, H217O, and saline) were administered to excised pig eye specimens. The samples were scanned using T1 mapping, T2 mapping, 3D T2-weighted (echo times (TE): 500, 3200, and 4500 ms), a half-Fourier single-shot turbo-spin echo sequence (HASTE; TE: 440 and 3000 ms), and 3D-real inversion-recovery before eye drops administration. Subsequently, we used a plastic dropper to drop a 0.5 mL solution each, and images were obtained up to 26 h later. Temporal changes in the T1 and T2 values of the anterior chamber and vitreous cavity were compared. The other sequences were evaluated by determining temporal signal changes as signal intensity ratio (SIR) compared to "No drop." The T1 and T2 values of samples treated with gadobutrol and H217O decreased over time. The SIR of samples treated with gadobutrol and H217O showed remarkable changes in the 3D T2-weighted images, whereas no remarkable temporal changes were observed in the other solutions. Longer TEs resulted in remarkable changes. We demonstrated that visualization of distribution in the vitreous cavity via eye drops could be achieved with excised pig eyes using gadobutrol and H217O, but not with ophthalmic solutions. Ultra-heavily T2-weighted sequences may be promising for the early and highly sensitive visualization of the intraocular distribution of eye drops.

Secondary Angle Closure Caused by Anterior Displacement of Capsular Tension Ring and Intraocular Lens Due to Aqueous Misdirection.

A capsular tension ring (CTR) is used for support to stabilize the capsular bag and intraocular lens (IOL) during and after cataract surgery. Although complications involving the CTR-IOL complex are not uncommon, cases of anterior displacement leading to complications are rare. This report presents a case of secondary angle closure caused by anterior displacement of the CTR-IOL complex due to aqueous misdirection and reports unique findings noted on anterior segment optical coherence tomography (AS-OCT). The patient, a 69-year-old woman, developed an acute angle closure crisis (AACC) and underwent cataract surgery with the implantation of a CTR and IOL. Post-surgery, there was an improvement in the central depth of the anterior chamber, but the patient experienced intermittent spikes in intraocular pressure. AS-OCT revealed a flat center of the iris and a closed anterior chamber angle which are plateau-iris-like findings. Secondary angle closure was caused by the CTR-IOL complex which was anteriorly displaced and pushed the peripheral iris owing to aqueous misdirection syndrome. Three weeks after the initial surgery, the patient underwent CTR removal, anterior vitrectomy, and intrascleral lens fixation. After the second surgery, intraocular pressure was normalized without any medications, and the anterior chamber angle was enlarged. This case provides a better understanding of secondary angle closure caused by the anterior displacement of the CTR-IOL complex and highlights the importance of AS-OCT in the detection of such complications.

Relation between a history of glaucoma and subjective happiness: the JPHC-Next study.

OBJECTIVE: This population-based, cross-sectional study was performed to investigate the relationship between a history of glaucoma and subjective happiness. METHODS AND ANALYSIS: We conducted a cross-sectional questionnaire-based survey of 92 397 Japanese men and women aged 40-74 who participated in the Japan Public Health Center-based Prospective Study for the Next Generation study. A multivariable logistic regression model was used to estimate the ORs of glaucoma associated with subjective happiness and their two-sided 95% CIs. RESULTS: Among 40 727 men and 51 670 women, 1733 participants (635 men, 1098 women) had a history of glaucoma. The odds of unhappiness in male participants with a history of glaucoma were higher (OR 1.26; 95% CI 1.05 to 1.51) than in female participants (OR 1.05; 95% CI 0.90 to 1.23). In a subgroup analysis stratified by age, among participants with a history of glaucoma, males in the younger group (40-59 years) showed the most robust association with unhappiness (OR 1.40; 95% CI 1.04 to 1.88). CONCLUSIONS: These findings suggest that a history of glaucoma is related with subjective unhappiness, especially in men.

Neuroprotective role of superoxide dismutase 1 in retinal ganglion cells and inner nuclear layer cells against N-methyl-d-aspartate-induced cytotoxicity.

The N-methyl-d-aspartate (NMDA) receptor-induced apoptosis is implicated in the pathological mechanisms of neural tissues, increasing the release of reactive oxygen species (ROS), resulting in a type of apoptotic cell death called excitotoxicity. Although intrinsic mechanisms to remove ROS, such as antioxidant enzymes, are provided by the tissue, the association between NMDA-induced excitotoxicity and antioxidative enzymes is not well understood. In this study, we focused on superoxide dismutase 1 (SOD1), an antioxidant enzyme, and investigated the role of SOD1 in the NMDA-induced neuronal cell death in the retina. NMDA was intravitreally injected into wild-type (WT) and SOD1 total knock-out (SOD1-deficient) mice. The number of TUNEL-positive cells in the retinal ganglion cell layer (GCL) and inner nuclear layer (INL) counted in the retinal sections and flatmount retinas were significantly higher in the SOD1-deficient mice than the WT mice after NMDA injection. Visual function assessed by dark-adapted electroretinogram (ERG) showed that the amplitudes of a-wave, b-wave, and oscillatory potential 2 were significantly reduced in the NMDA-injected SOD1-deficient mice. The level of ROS in the GCL and INL, measured using dihydroethidium, and the number of positive cells for γ-H2AX, a marker for DNA double strand breaks, and 8-OHdG, a marker for DNA oxidation, in the GCL were significantly increased in the SOD1-deficient mice after NMDA injection. We also measured mRNA and protein levels of SOD1 and SOD2 in the retina of WT mice, to find that mRNA and protein levels of SOD1, but not SOD2, were significantly reduced after NMDA injection. SOD1 deficiency exacerbated NMDA-induced damage to the inner retinal neurons, and NMDA reduced SOD1 levels in the retina of WT mice. Therefore, SOD1 protected retinal neurons against NMDA-induced retinal neurotoxicity, and NMDA-induced SOD1 reduction may be involved in neuronal vulnerability to excitotoxicity.

Ocular surface complications after trabeculectomy: incidence, risk factors, time course and prognosis.

PURPOSE: To investigate the incidence, risk factors, time course and prognosis of ocular surface complications after trabeculectomy. PROCEDURES: This is a retrospective, case-control study. Data on 399 consecutive patients who underwent trabeculectomy between 1999 and 2009 were evaluated. Cases of postoperative corneal epithelial defects, filamentary keratitis and dellen were evaluated. The risk factors for these ocular surface complications were analyzed with a logistic regression model. RESULTS: Corneal epithelial defects were found in 44 of the 399 patients (11%), filamentary keratitis in 12 patients (3%) and dellen in 7 patients (2%). Dellen required surgical intervention at a statistically significantly higher rate than corneal epithelial defects or filamentary keratitis (p = 0.0001, Fisher's exact test). The significant risk factors for these ocular surface complications were found to be a history of preoperative superficial punctate keratopathy (odds ratio, OR: 2.10, 95% confidence interval, CI: 1.25-3.51, p = 0.005) and a history of diabetes mellitus (OR: 1.69, 95% CI: 1.02-2.81, p = 0.04). CONCLUSIONS: Ocular surface complications following trabeculectomy are not rare. The biggest risk factors for these complications were found to be a history of preoperative superficial punctate keratopathy and a history of diabetes mellitus. Surgery is likely to be required for the treatment of dellen.

Implantation of diffractive extended depth-of-focus intraocular lenses in normal tension glaucoma eyes: A case series.

Purpose: Implantation of presbyopia-correcting intraocular lenses (IOLs) has not been advised for glaucomatous eyes because of the risk of decreased contrast sensitivity with progress of glaucoma. Extended depth-of-focus (EDF) IOLs have been reported to provide comparable postoperative visual function and influence on the visual field to monofocal IOLs. Methods: This case series was a retrospective medical record review of 16 eyes of 10 patients who had normal tension glaucoma (NTG) with no central visual field defects and underwent cataract surgery with implantation of diffractive EDF IOLs. At 3 months postoperatively, distance-corrected visual acuities (DCVAs) at distances of 5, 1, and 0.5 m and photopic contrast sensitivity were examined. Automated perimetry using the 30-2 Swedish interactive threshold algorithm was also performed, and the mean variance (MD) values, mean deviation values at the central four points (central MD), and foveal threshold were recorded. Results: The mean age of the patients (5 men, 5 women) was 66.5 years. Over 80% of eyes obtained DCVAs of 20/20, 20/20, and 20/25 at 5 m, 1 m, and 0.5 m, respectively. Whereas 5 of 16 eyes were categorized as severe by the Hodapp-Parrish-Anderson classification, postoperative contrast sensitivity was within the normal range, except for 4 eyes at 18 cycles per degree. Conclusions and importance: In this case series, the postoperative visual functions of NTG patients with EDF IOLs were almost comparable to those of normal eyes with the same IOLs, which demonstrated that the use of EDF IOLs for controlled NTG eyes would be permissible. While careful patient selection and follow-up for NTG progress are important, further investigations are necessary for confirming the safety and exploring the selection criteria.

Associations between fatty acid intake and diabetic retinopathy in a Japanese population.

Residents of Chikusei City, aged 40-74 years, underwent systemic and ophthalmological screening, and participants with diabetes were included in this analysis. Dietary intake was assessed using a food frequency questionnaire and calculated as a percentage of the total energy. The presence of diabetic retinopathy (DR) was defined as Early Treatment Diabetic Retinopathy Study levels ≥ 20 in either eye. The association between dietary fatty acid intake and DR has been examined in a cross-sectional study. Among the 647 diabetic participants, 100 had DR. The mean total fat and saturated fatty acid (SFA) intakes were 22.0% and 7.3% of the total energy intake, respectively. After adjusting for potential confounders, the highest quartiles of total fat and SFA intake were positively associated with the presence of DR compared with the lowest quartiles (odds ratios (95% confidence intervals), 2.61 (1.07-6.39), p for trend = 0.025, and 2.40 (1.12-5.17), p for trend = 0.013, respectively). No significant associations were found between DR prevalence and monounsaturated or unsaturated fatty acid intake. These results suggest that a high intake of fat and SFA may affect the development of DR, even in individuals whose total fat intake is generally much lower than that of Westerners.

Association Between Fatty Acid Intakes and Age-Related Macular Degeneration in a Japanese Population: JPHC-NEXT Eye Study.

Purpose: To determine the associations between fatty acid intakes and the prevalence of age-related macular degeneration (AMD) under a population-based cross-sectional study. Methods: Residents of Chikusei City aged ≥40 years underwent systemic and eye screening. AMD was graded according to a modified version of the Age-Related Eye Disease Study classification. Dietary intake was assessed using a food frequency questionnaire and was adjusted for total energy intake. Results: Altogether, 10,788 eyes of 5394 participants, 2116 men (mean [standard deviation (SD)] age, 62.4 [9.4] years) and 3278 women (60.6 [9.5] years), were included. The mean daily total fat intakes were 52.8 g and 59.0 g in men and women, respectively. After adjustments for potential confounders, saturated fatty acid (SFA) intake was inversely associated with the prevalence of any AMD in men (for each energy-adjusted 1-SD increase: odds ratio [OR], 0.86; 95% confidence interval [CI], 0.74-1.00). Significant trends were found for decreasing odds ratios of AMD with increasing SFA, monounsaturated fatty acid (MUFA), and polyunsaturated fatty acid (PUFA) intake (P for trend = 0.02, 0.04, and 0.04, respectively). In women, only a significant association was observed between the second quartile of linolenic acid intake and the prevalence of any AMD (OR, 0.78; 95% CI, 0.62-0.99). Conclusions: We found an inverse association of SFA intake and a weak inverse association of MUFA and PUFA intakes with the prevalence of any AMD in a Japanese population. Translational Relevance: Adequate fatty acid intake may be necessary to prevent or decelerate AMD.